Search results for: spread of drugs

Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: Tawatchai Apidechkul

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This operational research was conducted and divided into two phases: the first phase aimed to determine the risk behaviors used a cross-sectional study design, following by the community participatory research design to develop the HIV/AIDS preventive model among the Akha youths. The instruments were composed of completed questionnaires and assessment forms that were tested for validity and reliability before use. Study setting was Jor Pa Ka and Saen Suk Akha villages, Mae Chan District, Chiang Rai, Thailand. Study sample were the Akha youths lived in the villages. Means and chi-square test were used for the statistical testing. Results: Akha youths in the population mobilization villages live in agricultural families with low income and circumstance of narcotic drugs. The average age was 16 (50.00%), 51.52% Christian, 48.80% completed secondary school, 43.94% had annual family income of 30,000-40,000 baht. Among males, 54.54% drank, 39.39% smoked, 7.57% used amphetamine, first sexual intercourse reported at 14 years old, 50.00% had 2-5 partners, 62.50% had unprotected sex (no-condom). Reasons of unprotected sex included not being able to find condom, unawareness of need to use condoms, and dislike. 28.79% never been received STI related information, 6.06% had STI. Among females, 15.15% drank, 28.79% had sexual intercourse and had first sexual intercourse less than 15 year old. 40.00% unprotected sex (no-condom), 10.61% never been received STI related information, and 4.54% had STI. The HIV/AIDS preventive model contained two components. Peer groups among the youths were built around interests in sports. Improving knowledge would empower their capability and lead to choices that would result in HIV/AIDS prevention. The empowering model consisted of 4 courses: a. human reproductive system and its hygiene, b. risk-avoid skills, family planning, and counseling techniques, c. HIV/AIDS and other STIs, d. drugs and related laws and regulations. The results of the activities found that youths had a greater of knowledge and attitude levels for HIV/AIDS prevention with statistical significance (χ2-τεστ= 12.87, p-value= 0.032 and χ2-τεστ= 9.31, p-value<0.001 respectively). A continuous and initiative youths capability development program is the appropriate process to reduce the spread of HIV/AIDS in youths, particularly in the population who have the specific of language and culture.

Keywords: AIV/AIDS, preventive program, effective, hill tribe

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Authors: Ajit Kumar Sah, Rajesh Kumar Jha, Phoolgen Sah, Dev Kumar Shah

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Older individuals often suffer from multiple systemic diseases and are particularly more vulnerable to potentially inappropriate medicine prescribing. Inappropriate medication can cause serious medical problem for the elderly. The purpose of this study was to determine the prevalence of potentially inappropriate medicine (PIM) prescribing in older Nepalese patients in a medicine outpatient department. Beers’ criteria are the most widely used tools to assess PIM to elderly patients. Prospective observational analysis of drugs prescribed in medicine out-patient department (OPD) of a hospital of Bharatpur, Chitwan, Nepal during November 2011 to October 2012 to 869 older adults aged 65 years and above. The use of potentially inappropriate medications (PIM) in elderly patients was analyzed using Beers Criteria updated to 2013. In the 869 patients included the average number of drugs prescribed per prescription was 5.56. The most commonly used drugs were atenolol (24.3%), amlodipine (23.16%), paracetamol (17.6%), salbutamol (15.72%) and vitamin B complex (13.26%). The total number of medications prescribed was 4833. At least one instance of PIM was experienced by approximately 26.3% of patients when evaluated using the Beers criteria. Potentially inappropriate medications are highly prevalent among older patients attending medical OPD and are associated with a number of medications prescribed. Further research is warranted to study the impact of PIMs towards health-related outcomes in these elderly.

Keywords: Beers criteria, elderly, polypharmacy, potentially inappropriate medicines

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Authors: Dwi Yulian Fahruddin Shah, Salman Al Farizi, Elyada Ahastari Liunome

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Indonesia is a multicultural society. A wide variety of arts and culture spread throughout in all of part of Indonesia with natural appearance will cause the social behavior differentiation. Similarly, with Tengger people's lives also have different social behaviors that distinguish them from other ethnic groups spread across the Indonesian archipelago. Tengger tribe has an appropriate ethic to build nation character. If all the people of Indonesia who heterogeneous and multicultural can understand, and follow the example of ethical behavior of Tengger tribe, it will be a force in the development of the character of the nation in this modern and globalization era.

Keywords: Tengger tribe, national character, ethics society, Indonesia

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Authors: Asmaa Mandour, Ramzia El-Bagary, Asmaa El-Zaher, Ehab Elkady

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Background: An UHPLC (ultra high performance liquid chromatography) method for the simultaneous determination of norfloxacin (NOR), metronidazole (MET) and tinidazole (TNZ) using monolithic column is presented. Purpose: The method is considered an environmentally friendly method with relatively low organic composition of the mobile phase. Methods: The chromatographic separation was performed using Phenomenex® Onyex Monolithic C18 (50mmx 20mm) column. An elution program of mobile phase consisted of 0.5% aqueous phosphoric acid : methanol (85:15, v/v). Where elution of all drugs was completed within 3.5 min with 1µL injection volume. The UHPLC method was applied for the stability indication of NOR in the presence of its acid degradation product ND. Results: Retention times were 0.69, 1.19 and 3.23 min for MET, TNZ and NOR, respectively. While ND retention time was 1.06 min. Linearity, accuracy, and precision were acceptable over the concentration range of 5-50µg mL-1for all drugs. Conclusions: The method is simple, sensitive and suitable for the routine quality control and dosage form assay of the three drugs and can also be used for the stability indication of NOR in the presence of its acid degradation product.

Keywords: antibacterial, monolithic cilumn, simultaneous determination, UHPLC

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Authors: Luphumlo Ncanywa, Paul Watts

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Malaria is a disease that kills approximately one million people annually. Children and pregnant women in sub-Saharan Africa lost their lives due to malaria. Malaria continues to be one of the major causes of death, especially in poor countries in Africa. Decrease the burden of malaria and save lives is very essential. There is a major concern about malaria parasites being able to develop resistance towards antimalarial drugs. People are still dying due to lack of medicine affordability in less well-off countries in the world. If more people could receive treatment by reducing the cost of drugs, the number of deaths in Africa could be massively reduced. There is a shortage of pharmaceutical manufacturing capability within many of the countries in Africa. However one has to question how Africa would actually manufacture drugs, active pharmaceutical ingredients or medicines developed within these research programs. It is quite likely that such manufacturing would be outsourced overseas, hence increasing the cost of production and potentially limiting the full benefit of the original research. As a result the last few years has seen major interest in developing more effective and cheaper technology for manufacturing generic pharmaceutical products. Micro-reactor technology (MRT) is an emerging technique that enables those working in research and development to rapidly screen reactions utilizing continuous flow, leading to the identification of reaction conditions that are suitable for usage at a production level. This emerging technique will be used to develop antimalarial drugs. It is this system flexibility that has the potential to reduce both the time was taken and risk associated with transferring reaction methodology from research to production. Using an approach referred to as scale-out or numbering up, a reaction is first optimized within the laboratory using a single micro-reactor, and in order to increase production volume, the number of reactors employed is simply increased. The overall aim of this research project is to develop and optimize synthetic process of antimalarial drugs in the continuous processing. This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs on a worldwide scale, with a particular emphasis on Africa in the first instance. The research will determine the best chemistry and technology to define the lowest cost manufacturing route to pharmaceutical products. We are currently developing a method to synthesize Lumefantrine in continuous flow using batch process as bench mark. Lumefantrine is a dichlorobenzylidine derivative effective for the treatment of various types of malaria. Lumefantrine is an antimalarial drug used with artemether for the treatment of uncomplicated malaria. The results obtained when synthesizing Lumefantrine in a batch process are transferred into a continuous flow process in order to develop an even better and reproducible process. Therefore, development of an appropriate synthetic route for Lumefantrine is significant in pharmaceutical industry. Consequently, if better (and cheaper) manufacturing routes to antimalarial drugs could be developed and implemented where needed, it is far more likely to enable antimalarial drugs to be available to those in need.

Keywords: antimalarial, flow, lumefantrine, synthesis

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Authors: Takashi Kaminagayoshi, Shigeyuki Haruyama

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To improve the manufacturing efficiency of biologics, such as antibody drugs, a quality engineering framework was designed. Within this framework, critical steps and parameters in the manufacturing process were studied. Identification of these critical steps and critical parameters allows a deeper understanding of manufacturing capabilities, and suggests to process development department process control standards based on actual manufacturing capabilities as part of a PDCA (plan-do-check-act) cycle. This cycle can be applied to each manufacturing process so that it can be standardized, reducing the time needed to establish each new process.

Keywords: antibody drugs, biologics, manufacturing efficiency, PDCA cycle, quality engineering

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Authors: Celestina Omoso Isiramen

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The influence of witchcraft belief on disease causation, cure and public health system in Nigeria cannot be underrated. This paper investigated the nexus between witchcraft phenomenon and health-seeking behaviour of HIV sufferers in Edo state, Nigeria. Survey methodology was adopted and stratified random sampling technique was employed in the selection of 600 sample group spread into 200 HIV sufferers, 200 spiritual healers and 200 bio-medics from the three Senatorial districts of the state. Data were collected through the use of structured questionnaire and in-dept interview and analyzed using simple percentage and frequency. Major findings were: belief in witchcraft significantly influenced the people’s perception of HIV causation and wellness and this impacted adversely on public health-care. Poverty, ignorance and dearth of retroviral drugs enhanced the people’s recourse to spiritual healers. Collaboration between spiritual healing techniques and biomedicine was recommended as panacea for curbing HIV/AIDS related morbidity and mortality. It concluded that socio-economic problems must be addressed while the importance of integrating the values of spiritual healing into biomedicine cannot be overstressed.

Keywords: biomedicine, health care, HIV/AIDS, spirituality, witchcraft

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Authors: Moetazza M. Al-Shafei, Hala Abdel Karim, Eitedal M. Daoud, Hassan Zaki Hassuna

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Epilepsy is a common neurological disorder affecting all age groups. It is one of the world's most prevalent non-communicable diseases. Increased evidence suggesting that long term usage of anti-epileptic drugs can have adverse effects on bone mineralization and bone molding .Aiming to study these effects and to give guide lines to support bone health through early intervention. From Neurology Out-Patient Clinic kaser Elaini University Hospital, 60 Patients were enrolled, 40 patients on antiepileptic drugs for at least two years and 20 controls matched with age and sex, epileptic but before starting treatment both chosen under specific criteria. Patients were divided into four groups, three groups with monotherapy treated with either Phynetoin, Valporic acid or Carbamazipine and fourth group treated with both Valporic acid and Carbamazipine. Estimation of serum Carboxy-Terminal Telopeptide of Type I- Collagen(ICTP) bone resorption marker, serum 25(OH )vit D3, calcium ,magnesium and phosphorus were done .Results showed that all patients on AED had significant low levels of 25(OH) vit D3 (p<0.001) ,with significant elevation of ICTP (P<0.05) versus controls. In group treated with Phynotoin highly significant elevation of (ICTP) marker and decrease of both serum 25(OH) vit D3 (P<0, 0001) and serum calcium(P<0.05)versus control. Double drug group showed significant decrease of serum 25(OH) vit D3 (P<0.0001) and decrease in Phosphorus (P<0.05) versus controls. Serum magnesium showed no significant differences between studied groups. We concluded that Anti- epileptic drugs appears to be an aggravating factor on bone mineralization ,so therapeutically it can be worth wile to supplement calcium and vitamin D even before initiation of antiepileptic therapy. ICTP marker can be used to evaluate change in bone resorption before and during AED therapy.

Keywords: antiepileptic drugs, bone minerals, carboxy teminal telopeptidetype-1-collagen bone resorption marker, vitamin D

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Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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Authors: V. Surena, B. Nazemisalman, F. Noghrehkar

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Introduction: Gingival overgrowth (GO) is a common side effect involving users of antiepileptic, immunosuppressive and calcium channel blocker drugs. Cyclosporine and phenytoin are amongst the most widely used drugs associated with GO. Gingival fibroblasts seem to have a significant role in the production of certain enzymes after administration of the drugs contributing to GO. Previous studies have shown a higher prevalence of GO in children and adolescents. The aim of this study was to compare normal human gingival fibroblasts with those exposed to Cyclosporine or phenytoin in measuring the production levels of certain enzymes that could have a possible role in GO. Methods: samples were obtained from the gingival biopsies of seven adult and seven children and were cultured into plates. With the growth of fibroblast cells, they were treated with or without either Cyclosporine or phenytoin. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the expressed levels of R-EGF, cathepsin B,L, Lysyl oxidase, COL1, TGF β1, MMP-1,2, and TIMP1. Results: according to RT-PCR analyses, the expressed levels of R-EGF, cathepsin B, L, Lysyl oxidase, COL1, TGF β1, MMP-1, 2 and TIMP1 were affected by Cyclosporine and phenytoin. TGF-β1, TIMP, Cathepsin B and EGF showed comparable values in the adult and pediatric groups. Conclusions: Different expressed levels of enzymes after treatment of the gingival fibroblasts of adults and pediatrics with phenytoin or Cyclosporine could be the reason for the higher severity of GO in children. More studies need to be performed on the pathogenesis of GO at different age groups.

Keywords: cyclosporine, fibroblasts, phenytoin, gingivae

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Authors: Vishal Bhatnagar

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The objective of this study is to compare the efficacy of epidural analgesia of two amide local anesthetics, ropivacaine and levobupivacaine, with fentanyl for postoperative analgesia in major abdominal surgery CRS+HIPEC. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) are done for primary peritoneal malignancies or peritoneal spread of malignant neoplasm. CRS and HIPEC are considered one of the most painful surgery among all major abdominal surgeries. Poorly managed postoperative pain elevates stress, increases anxiety, causes prolonged Hospital stay, increases opioid requirement and side effects, increases the cost of treatment and psychological effects on patient and family. It affects the quality of life of patients. The epidural technique provides better postoperative analgesia, earlier recovery of bowel function, fewer side effects, higher patient satisfaction, and an improvement in life quality in the postoperative days after abdominal surgery than other analgesic techniques.

Keywords: HIPEC, postoperative analgesia, cytoreductive surgery, VAS score, rescue analgesia

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Authors: Ali Musbah Mohamed Elwahishi

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Democracy is demand for the majority of people in the whole world, Specifically in the regions that are still outside the democratic life such as Libya and other Arab countries. Although democracy has spread across the world through three waves of democratization, Libya is still outside the democratic process, even recently its regime has changed. The challenges of democracy in Libya are not new, they represent accumulations over time that impeded to achieve this goal. This paper concludes that the absence of democracy in Libya because of set of factors that include: colonial legacy, oil wealth, the lack of institutions, the lack of political parties, tribal factor and recently the spread of the armed groups. These factors prevented Libya to be democratic state whether during King Idris’, Qaddafi’s or even after Qaddafi rule.

Keywords: the failure of democracy, political transition, the lack of institutions, Libya, Arab countries

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Authors: Jay Ananth

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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.

Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development

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Authors: Abhishek Pandey

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Capping and lamination are the most common tablet defects with poorly compressible drugs the common example of that Ibuprofen and Acetaminophen. Generally both these drugs are compressed by wet granulation method which is very time consuming process Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis Acetaminophen used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression technique and their evaluation. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimize formulation nine different formulations were generated among them batch F5, F6, F7 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of evaluation parameters.

Keywords: capping, lamination, tablet defects, direct compression

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Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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Authors: Maryam Davodi-Far

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Although sustainability offers a vision to preserve the earth’s resources while sustaining life on earth, there tends to be injustice and disparity in how resources are allocated across the globe. As such, the question that arises is whom will sustainability benefit? Will the rich grow richer and the poor become worse off? Is there a way to find balance between sustainability and still implement and achieve success with distributive justice theories? One of the facets of justice is distributive justice; the idea of balancing benefits and costs associated with the way in which we disseminate and consume goods. Social justice relies on how the cost and burdens of our resource allocation can be done reasonably and equitably and spread across a number of societies, and within each society spread across diverse groups and communities. In the end, the question is how to interact with the environment and diverse communities of today and of those communities of the future.

Keywords: consumerism, sustainability, sustainable development, social justice, social equity, distributive justice

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Authors: A. Julio, R. Caparica, S. Costa Lima, S. Reis, J. G. Costa, P. Fonte, T. Santos De Almeida

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The Mycobacterium leprae causes a chronic and infectious disease called leprosy, which the most common symptoms are peripheral neuropathy and deformation of several parts of the body. The pharmacological treatment of leprosy is a combined therapy with three different drugs, rifampicin, clofazimine, and dapsone. However, clofazimine and dapsone have poor solubility in water and also low bioavailability. Thus, it is crucial to develop strategies to overcome such drawbacks. The use of ionic liquids (ILs) may be a strategy to overcome the low solubility since they have been used as solubility promoters. ILs are salts, liquid below 100 ºC or even at room temperature, that may be placed in water, oils or hydroalcoholic solutions. Another approach may be the encapsulation of drugs into polymeric nanoparticles, which improves their bioavailability. In this study, two different classes of ILs were used, the imidazole- and the choline-based ionic liquids, as solubility enhancers of the poorly soluble antileprotic drugs. Thus, after the solubility studies, it was developed IL-PLGA nanoparticles hybrid systems to deliver such drugs. First of all, the solubility studies of clofazimine and dapsone were performed in water and in water: IL mixtures, at ILs concentrations where cell viability is maintained, at room temperature for 72 hours. For both drugs, it was observed an improvement on the drug solubility and [Cho][Phe] showed to be the best solubility enhancer, especially for clofazimine, where it was observed a 10-fold improvement. Later, it was produced nanoparticles, with a polymeric matrix of poly(lactic-co-glycolic acid) (PLGA) 75:25, by a modified solvent-evaporation W/O/W double emulsion technique in the presence of [Cho][Phe]. Thus, the inner phase was an aqueous solution of 0.2 % (v/v) of the above IL with each drug to its maximum solubility determined on the previous study. After the production, the nanosystem hybrid was physicochemically characterized. The produced nanoparticles had a diameter of around 580 nm and 640 nm, for clofazimine and dapsone, respectively. Regarding the polydispersity index, it was in agreement of the recommended value of this parameter for drug delivery systems (around 0.3). The association efficiency (AE) of the developed hybrid nanosystems demonstrated promising AE values for both drugs, given their low solubility (64.0 ± 4.0 % for clofazimine and 58.6 ± 10.0 % for dapsone), that prospects the capacity of these delivery systems to enhance the bioavailability and loading of clofazimine and dapsone. Overall, the study achievement may signify an upgrading of the patient’s quality of life, since it may mean a change in the therapeutic scheme, not requiring doses of drug so high to obtain a therapeutic effect. The authors would like to thank Fundação para a Ciência e a Tecnologia, Portugal (FCT/MCTES (PIDDAC), UID/DTP/04567/2016-CBIOS/PRUID/BI2/2018).

Keywords: ionic liquids, ionic liquids-PLGA nanoparticles hybrid systems, leprosy treatment, solubility

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Authors: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: Stanely Nsubuga

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Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.

Keywords: People who Use Drugs, transition, injection drug use, Uganda

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Monika Szpringer, Aneta Pawlinska

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Adverse childhood experiences are linked to various types of health and adapt problems at different stages of life. They include various types of abuse, neglect, and dysfunctional environment. They have an unfavorable impact on the development of a child and his future functioning in society. Adolescents who were exposed to bad treatment may suffer from health problems during adulthood, like chronic diseases, psychological disorders, drug addiction, and suicide attempts. Objective: The aim of the project is to assess the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs. Material And Methods: The research was carried out in the period from March to December 2018 in Mazowieckie, Świętokrzyskie, Łódzkie, and Lubelskie Voivodship. The group consisted of 600 people aged 16-18 (M=16,58; SD=0, 78), men (63,2%) aged 16-18 (M=16,60;SD= 0,78) and women (35,5%) aged 16-18 (M16,55;SD=0,79). Participants included residents from Youth Educational Centers and Youth Sociotherapy Centers. Each participant filled in Author's Questionnaire, Adverse Childhood Questionnaire, then Courtland Emotional Control Scale-CECS and Generalized Self Efficacy Scale-GSES. Results and conclusions: The most common adverse experiences, according to teenagers, were family abuse, divorce/separation/parent's death, overuse of alcohol or drugs by an inmate, and emotional neglect. Adolescents who suffered from five to twelve adverse experiences had a higher level of depression's control. Adverse childhood experiences have an importance for the level of anger and depression's control among teenagers taking drugs. The greatest importance of the level of anger's control has emotional neglect. A higher level of emotional neglect is linked to a lower ability to control anger. The greatest importance of the level of depression's control has physical abuse and emotional neglect. The higher physical abuse during childhood, and the higher frequency of emotional neglect, the bigger the depression's control. The sense of efficacy in the group of people who suffered from one to four adverse experiences is close to the sense of efficacy that suffered people from five to twelve adverse experiences. The most important factor lowering the sense of one's efficacy was the intensification of sexual abuse. It was confirmed that the intensification and frequency of adverse childhood experiences were higher among women than men. Women also characterized lower anger control and greater depression's control. The authors’ own analyses confirmed the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs.

Keywords: adolescences, adverse childhood experiences, coping with emotions, drugs

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Huafeng Wei

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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Hassan M. Albishri, Fatimah Al-Shehri, Deia Abd El-Hady

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Among the analytical techniques, reverse phase liquid chromatography (RPLC) is currently used in pharmaceutical industry. Ecofriendly analytical chemistry offers the advantages of decreasing the environmental impact with the advantage of increasing operator safety which constituted a topic of industrial interest. Recently, ionic liquids have been successfully used to reduce or eliminate the conventional organic toxic solvents. In the current work, a simple and ecofriendly ionic liquid modified RPLC (IL-RPLC) method has been firstly developed and compared with RPLC under acidic and neutral mobile phase conditions for simultaneous determination of atorvastatin-calcium, rosuvastatin and simvastatin. Several chromatographic effective parameters have been changed in a systematic way. Adequate results have been achieved by mixing ILs with ethanol as a mobile phase under neutral conditions at 1 mL/min flow rate on C18 column. The developed IL-RPLC method has been validated for the quantitative determination of drugs in pharmaceutical formulations. The method showed excellent linearity for analytes in a wide range of concentrations with acceptable precise and accurate data. The current IL-RPLC technique could have vast applications particularly under neutral conditions for simple and greener (bio)analytical applications of pharmaceuticals.

Keywords: ionic liquid, RPLC, anti-hyperlipidemic drugs, ecofriendly

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Authors: R. Mehta, M. Ghogomu, B. Schoel

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Reports appeared in 2020 about China detecting SARS-Cov-2 (Covid-19) on frozen meat, shrimp, and food packaging material. In this study, we examined the use of swabs for the detection of Covid-19 on meat samples, and chicken breast (CB) was used as a model. Methods: Heat inactivated SARS-Cov-2 virus (IV) from Microbiologics was loaded onto the CB, swabbing was done, and the recovered inactivated virus was subjected to the Machery & Nagel NucleoSpin RNAVirus kit for RNA isolation according to manufacturer's instructions. For RT-PCR, the IDT 2019-nCoV RUO Covid-19 test kit was used with the Taqman Fast Virus 1-step master mix. The limit of detection (LOD) of viral load recovered from the CB was determined under various conditions: first on frozen CB where the IV was introduced on a defined area, then on frozen CB, with IV spread-out, and finally, on thawed CB. Results: The lowest amount of IV which can be reliably detected on frozen CB was a load of 1,000 - 2,000 IV copies where the IV was loaded on one spot of about 1 square inch. Next, the IV was spread out over a whole frozen CB about 16 square inches. The IV could be recovered at a lowest load of 4,000 to 8,000 copies. Furthermore, the effects of temperature change on viral load recovery was investigated i.e., if raw unfrozen meat became contaminated and remains for 1 hour at 4°C or gets refrozen. The amount of IV recovered successfully from CB kept at 4°C and the refrozen CB was similar to the recovery gotten from loading the IV directly on the frozen CB. In conclusion, an assay using swabs was successfully established for the detection of SARS-Cov-2 on frozen or raw (unfrozen) CB with a minimal load of up to 8,000 copies spread over 16 square inches.

Keywords: assay, COVID-19, meat, SARS-Cov-2

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Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

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Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

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Authors: Jiří Barta

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The paper deals with simulation programs of spread of harmful substances. Air pollution has a direct impact on the quality of human life and environmental protection is currently a very hot topic. Therefore, the paper focuses on the simulation of release of harmful substances. The first part of article deals with perspectives and possibilities of implementation outputs of simulations programs into the system which is education and of practical training of the management staff during emergency events in the frame of critical infrastructure. The last part shows the practical testing and evaluation of simulation programs. Of the tested simulations software been selected Symos97. The tool offers advanced features for setting leakage. Gradually allows the user to model the terrain, location, and method of escape of harmful substances.

Keywords: Computer Simulation, Symos97, Spread, Simulation Software, Harmful Substances

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